Synthetic Supramolecular Signalling Systems

Samenvatting

Supramolecular architectures will be brought to the next level of complexity by merging them with engineered proteins in order to generate synthetic supramolecular signalling systems. There is considerable untapped potential in combining the unique structural and functional properties of proteins and supramolecular architectures to generate entirely novel types of molecular systems with enhanced functionality, for example via the bottom-up design of synthetic signalling systems. An important step towards realizing this potential is outlined in this proposal: the design, generation, and study of such signalling systems to understand, affect, and ultimately mimic biomolecular architectures. These systems will be the first prototypes of cell-like supramolecular signalling platforms, complementing biological systems with new functionalities, and enabling the development of signal amplification systems applicable to molecular diagnostics.
Three approaches to synthetic supramolecular signalling systems will be explored, each one complementary, either in the design of the synthetic supramolecular system or in the protein based signalling cascades under study. The formation of discrete protein assemblies using host-guest or protein-ligand interactions forms the basis of Topic 1, yielding ?plug-and-play? elements to generate signalling systems with feedback or sensing capabilities. In Topic 2 signalling proteins will be assembled and activated on extended supramolecular wires. Both supramolecular approaches will be applied in Topic 3 for the supramolecular activation of membrane protein signalling in a bio-orthogonal and reversible manner.
This proposal addresses a strong demand in the life sciences for novel ways to control signalling. This work will contribute new concepts, tools, and materials, applied to cells and for bioanalyte detection, will be of benefit to the biological community and ultimately contribute to the understanding of the complexity of life. New biochemical signal amplification systems are in demand by the molecular diagnostics community and a number of the proposed designs will be of benefit to this field.

Kenmerken

Projectnummer

724.014.002

Hoofdaanvrager

Prof. dr. ir. L. Brunsveld

Verbonden aan

Technische Universiteit Eindhoven, Faculteit Biomedische Technologie, Chemical Biology

Uitvoerders

Dr. M.A. Aléman Garcia, Prof. dr. ir. L. Brunsveld, Dr. R.G. Doveston, Ir. L.J.M. Lemmens, Ir. L.M. Stevens, Ir. P.J. de Vink, Ir. R.M.J.M. de Vries

Looptijd

01/09/2015 tot 31/08/2020